Cancer cachexia, a cancer-related symptom, is a complex metabolic condition characterized by the accelerated loss of skeletal muscle mass with or without concomitant loss of fat mass. Cancer cachexia occurs when muscle wasting leads to weight loss greater than 5% in 12 months or less. Muscle wasting may contribute to reduced quality of life (QoL) and shortened survival in patients with cancer. Cancer-associated weight loss is observed much more frequently with certain cancer types (e.g., gastrointestinal, pancreatic, lung, and colorectal cancers).
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. It usually grows and spreads more slowly than small cell lung cancer. There are three forms of NSCLC. Each form of non-small cell lung cancer has different kinds of cancer cells: (i) Adenocarcinomas are often found in an outer area of the lung; (ii) Squamous cell carcinomas are usually found in the center of the lung by an air tube (bronchus); (iii) Large cell carcinomas can occur in any part of the lung. They tend to grow and spread faster than the other two types. Other less common types of non-small cell lung cancer are: pleomorphic, carcinoid tumor, salivary gland carcinoma, and unclassified carcinoma.
Cancer cachexia is a multifactoral condition. In addition to accelerated loss of skeletal muscle and loss of weight, patients commonly present with fatigue, anorexia, anemia, decreased physical function, and an increase in inflammatory proteins, which may collectively contribute to physical disability and reduced QoL. This combination of clinical factors is, in part, responsible for the poor prognosis and increased mortality of patients with cancer cachexia. Importantly, patients with cancer who have diminished muscle mass also have poorer treatment outcomes and are less able to tolerate chemotherapy. Thus, cachexia and associated loss of muscle mass may have detrimental clinical consequences early in the course of a patient's malignancy, underscoring the importance of diagnosing and treating this condition at an early stage. Although significant weight loss is often a presenting symptom for patients with cancer cachexia, it usually occurs in advanced stages of the disease. The reduction in skeletal muscle mass occurs earlier in the disease and as a result is often undiagnosed, yet is the more intractable component of the wasting state. Unfortunately, current treatment options are limited and primarily offer only palliative support. Nutritional supplementation is commonly recommended but is unable to reverse the underlying catabolic cause(s) of wasting and cannot restore muscle mass; thus, this strategy has shown minimal benefit in ameliorating the decline of muscle mass and worsening of physical function. To date, there are no agents approved for the prevention or treatment of muscle wasting in cancer patients.
Agents that directly address the accelerated loss of skeletal muscle mass are currently being evaluated for use in the prevention and treatment of muscle wasting. Anabolic androgenic steroids have been shown to increase skeletal muscle and lean body mass (LBM); however, the relative lack of tissue specificity and associated side effects of these agents may limit their use. Selective androgen receptor modulators (SARMs) are a well-studied class of nonsteroidal, tissue-specific, androgen receptor agonists that have the potential to increase muscle and bone mass and improve physical function without unwanted effects on the prostate, skin, or hair, which are commonly associated with testosterone or other nonselective, synthetic anabolic steroids.
New innovative approaches are needed at both the basic science and clinical levels to develop compounds which are useful for treating, suppressing, inhibiting or reducing the incidence of muscle wasting in patients with cancer, treating loss of physical function due to cancer or cancer therapy (radiation, chemotherapy, surgery) and increasing their physical function; thereby improving quality of life of cancer patients.